Crohn's disease in endoscopic remission, obesity, and cases of high genetic risk demonstrates overlapping shifts in the colonic mucosal-luminal interface microbiome.

BACKGROUND: Crohn's disease (CD) patients demonstrate distinct intestinal microbial compositions and metabolic characteristics compared to unaffected controls. However, the impact of inflammation and underlying genetic risk on these microbial profiles and their relationship to disease phenotype are unclear. We used lavage sampling to characterize the colonic mucosal-luminal interface (MLI) microbiome of CD patients in endoscopic remission and unaffected controls relative to obesity, disease genetics, and phenotype. METHODS: Cecum and sigmoid colon were sampled from 110 non-CD controls undergoing screening colonoscopy who were stratified by body mass index and 88 CD patients in endoscopic remission (396 total samples). CD polygenic risk score (GRS) was calculated using 186 known CD variants. MLI pellets were analyzed by 16S ribosomal RNA gene sequencing, and supernatants by untargeted liquid chromatography-mass spectrometry. RESULTS: CD and obesity were each associated with decreased cecal and sigmoid MLI bacterial diversity and distinct bacterial composition compared to controls, including expansion of Escherichia/Shigella. Cecal and sigmoid dysbiosis indices for CD were significantly greater in obese controls than non-overweight controls. CD, but not obesity, was characterized by altered biogeographic relationship between the sigmoid and cecum. GRS was associated with select taxonomic shifts that overlapped with changes seen in CD compared to controls including Fusobacterium enrichment. Stricturing or penetrating Crohn's disease behavior was characterized by lower MLI bacterial diversity and altered composition, including reduced Faecalibacterium, compared to uncomplicated CD. Taxonomic profiles including reduced Parasutterella were associated with clinical disease progression over a mean follow-up of 3.7 years. Random forest classifiers using MLI bacterial abundances could distinguish disease state (area under the curve (AUC) 0.93), stricturing or penetrating Crohn's disease behavior (AUC 0.82), and future clinical disease progression (AUC 0.74). CD patients showed alterations in the MLI metabolome including increased cholate:deoxycholate ratio compared to controls. CONCLUSIONS: Obesity, CD in endoscopic remission, and high CD genetic risk have overlapping colonic mucosal-luminal interface (MLI) microbiome features, suggesting a shared microbiome contribution to CD and obesity which may be influenced by genetic factors. Microbial profiling during endoscopic remission predicted Crohn's disease behavior and progression, supporting that MLI sampling could offer unique insight into CD pathogenesis and provide novel prognostic biomarkers.

Management of pouch neoplasia: consensus guidelines from the International Ileal Pouch Consortium.

Surveillance pouchoscopy is recommended for patients with restorative proctocolectomy with ileal pouch-anal anastomosis in ulcerative colitis or familial adenomatous polyposis, with the surveillance interval depending on the risk of neoplasia. Neoplasia in patients with ileal pouches mainly have a glandular source and less often are of squamous cell origin. Various grades of neoplasia can occur in the prepouch ileum, pouch body, rectal cuff, anal transition zone, anus, or perianal skin. The main treatment modalities are endoscopic polypectomy, endoscopic ablation, endoscopic mucosal resection, endoscopic submucosal dissection, surgical local excision, surgical circumferential resection and re-anastomosis, and pouch excision. The choice of the treatment modality is determined by the grade, location, size, and features of neoplastic lesions, along with patients' risk of neoplasia and comorbidities, and local endoscopic and surgical expertise.

Treatment of pouchitis, Crohn's disease, cuffitis, and other inflammatory disorders of the pouch: consensus guidelines from the International Ileal Pouch Consortium.

Pouchitis, Crohn's disease of the pouch, cuffitis, polyps, and extraintestinal manifestations of inflammatory bowel disease are common inflammatory disorders of the ileal pouch. Acute pouchitis is treated with oral antibiotics and chronic pouchitis often requires anti-inflammatory therapy, including the use of biologics. Aetiological factors for secondary pouchitis should be evaluated and managed accordingly. Crohn's disease of the pouch is usually treated with biologics and its stricturing and fistulising complications can be treated with endoscopy or surgery. The underlying cause of cuffitis determines treatment strategies. Endoscopic polypectomy is recommended for large, symptomatic inflammatory polyps and polyps in the cuff. The management principles of extraintestinal manifestations of inflammatory bowel disease in patients with pouches are similar to those in patients without pouches.

Diagnosis and classification of ileal pouch disorders: consensus guidelines from the International Ileal Pouch Consortium.

Restorative proctocolectomy with ileal pouch-anal anastomosis is an option for most patients with ulcerative colitis or familial adenomatous polyposis who require colectomy. Although the construction of an ileal pouch substantially improves patients' health-related quality of life, the surgery is, directly or indirectly, associated with various structural, inflammatory, and functional adverse sequelae. Furthermore, the surgical procedure does not completely abolish the risk for neoplasia. Patients with ileal pouches often present with extraintestinal, systemic inflammatory conditions. The International Ileal Pouch Consortium was established to create this consensus document on the diagnosis and classification of ileal pouch disorders using available evidence and the panellists' expertise. In a given individual, the condition of the pouch can change over time. Therefore, close monitoring of the activity and progression of the disease is essential to make accurate modifications in the diagnosis and classification in a timely manner.

Association of Wearable Activity Monitors With Assessment of Daily Ambulation and Length of Stay Among Patients Undergoing Major Surgery.

Importance: Early postoperative ambulation is vital to minimizing length of stay (LOS), but few hospitals objectively measure ambulation to predict outcomes. Wearable activity monitors have the potential to transform assessment of postoperative ambulation, but key implementation data, including whether digitally monitored step count can identify patients at risk for poor efficiency outcomes, are lacking. Objectives: To define the distribution of digitally measured daily step counts after major inpatient surgical procedures, to assess the accuracy of physician assessment and ordering of ambulation, and to quantify the association of digitally measured step count with LOS. Design, Setting, and Participants: Prospective cohort study at Cedars-Sinai Medical Center, an urban tertiary referral center. Participants were patients undergoing 8 inpatient operations (lung lobectomy, gastric bypass, hip replacement, robotic cystectomy, open colectomy, abdominal hysterectomy, sleeve gastrectomy, and laparoscopic colectomy) from July 11, 2016, to August 30, 2017. Interventions: Use of activity monitors to measure daily postoperative step count. Main Outcomes and Measures: Operation-specific daily step count, daily step count by physician orders and assessment, and a prolonged LOS (>70th percentile for each operation). Results: Among 100 patients (53% female), the mean (SD) age was 53 (18) years, and the median LOS was 4 days (interquartile range, 3-6 days). There was a statistically significant increase in daily step count with successive postoperative days in aggregate (r = 0.55; 95% bootstrapped CI, 0.47-0.62; P < .001) and across individual operations. Ninety-five percent (356 of 373) of daily ambulation orders were "ambulate with assistance," although daily step counts ranged from 0 to 7698 steps (0-5.5 km) under this order. Physician estimation of ambulation was predictive of the median step count (r = 0.66; 95% bootstrapped CI, 0.59-0.72; P < .001), although there was substantial variation within each assessment category. For example, daily step counts ranged from 0 to 1803 steps (0-1.3 km) in the "out of bed to chair" category. Higher step count on postoperative day 1 was associated with lower odds of prolonged LOS from 0 to 1000 steps (odds ratio [OR], 0.63; 95% CI, 0.45-0.84; P = .003), with no further decrease in odds after 1000 steps (OR, 0.99; 95% CI, 0.75-1.30; P = .80). Conclusions and Relevance: In this study, digitally measured step count up to 1000 steps on postoperative day 1 was associated with lower probability of a prolonged LOS. Wearable activity monitors improved the accuracy of assessment of daily step count over the current standard of care, providing an opportunity to identify patients at risk for poor efficiency outcomes.

Colorectal cancer screening and surveillance in Crohn's colitis.

AIMS: To assess colonoscopic screening and surveillance for detecting neoplasia in patients with long-standing colonic Crohn's disease (CD). PATIENTS AND METHODS: Colonoscopy and biopsy records from patients with colonic CD were evaluated at the Cedars-Sinai Inflammatory Bowel Disease Center during a 17-year period (1992-2009). RESULTS: Overall, 904 screening and surveillance examinations were performed on 411 patients with Crohn's colitis (mean 2.2 examinations per patient). The screening and surveillance examinations detected neoplasia in 5.6% of the patient population; 2.7% had low-grade dysplasia (LGD) (n=11), 0.7% had high-grade dysplasia (HGD) (n=3), and 2.2% had carcinoma (anal carcinoma n=3; rectal carcinoma n=6). Mean age of CD diagnosis was 25.6±0.8 years in those with normal examinations, compared to 17.7±2.7 years (p<0.001) in those with HGD, 36.85±1.43 in those with LGD (p=0.021) and 28.32±3.24 years in those with any dysplasia/cancer (p=0.034). Disease duration in patients with normal examinations was 19.1±0.5 years, compared to 36.8±4.4 years (p<0.001) in HGD, 16.88±2.59 in those with LGD (p=0.253) and 30.68±4.03 years in those with any dysplasia/cancer (p=0.152). The mean interval between examinations was higher in HGD (31.5±9.4 months) compared to those with normal colonoscopies (12.92±1.250 months; p=0.002). CONCLUSIONS: We detected cancer or dysplasia in 5.6% of patients with long-standing Crohn's colitis enrolled in a screening and surveillance program. Younger age at diagnosis of CD, longer disease course, and greater interval between exams were risk factors for the development of dysplasia.